PROJECT ID: PRJNA754013

Data source SRA: PRJNA754013
Description Single-cell sequencing of the hypothalamus and pre-optic area of the zebrafish (Danio rerio) and Mexican tetra (Astyanax mexicanus)
Key word molecular architecture; origin; diversity; system; mouse; integration; cavefish; package
Publication Shafer, Maxwell ER, Ahilya N. Sawh, and Alexander F. Schier. "Gene family evolution underlies cell-type diversification in the hypothalamus of teleosts." Nature ecology & evolution 6.1 (2022): 63-76.
Abstract Hundreds of cell types form the vertebrate brain but it is largely unknown how similar cellular repertoires are between or within species or how cell-type diversity evolves. To examine cell-type diversity across and within species, we performed single-cell RNA sequencing of ~130,000 hypothalamic cells from zebrafish (Danio rerio) and surface and cave morphs of Mexican tetra (Astyanax mexicanus). We found that over 75% of cell types were shared between zebrafish and Mexican tetra, which diverged from a common ancestor over 150 million years ago. Shared cell types displayed shifts in paralogue expression that were generated by subfunctionalization after genome duplication. Expression of terminal effector genes, such as neuropeptides, was more conserved than the expression of their associated transcriptional regulators. Species-specific cell types were enriched for the expression of species-specific genes and characterized by the neofunctionalization of expression patterns of members of recently expanded or contracted gene families. Comparisons between surface and cave morphs revealed differences in immune repertoires and transcriptional changes in neuropeptidergic cell types associated with genomic differences. The single-cell atlases presented here are a powerful resource to explore hypothalamic cell types and reveal how gene family evolution and shifts in paralogue expression contribute to cellular diversity.


Dataset Information

Dataset ID Species Tissue / Organ Experiment type Sample Source dataset ID
1. PRJNA754013 (Choy surface) Astyanax mexicanus hypothalamus baseline male, female, adult, untreatment SRA: SRR15422711, SRR15422691
2. PRJNA754013 (Molino cave) Astyanax mexicanus hypothalamus baseline male, female, adult, untreatment SRA: SRR15422671, SRR15422704
3. PRJNA754013 (Pachon cave) Astyanax mexicanus hypothalamus baseline male, female, adult, untreatment SRA: SRR15422680, SRR15422698
4. PRJNA754013 (Tinaja cave) Astyanax mexicanus hypothalamus baseline male, female, adult, untreatment SRA: SRR15422699, SRR15422703
5. PRJNA754013 (zebrafish) Danio rerio hypothalamus baseline adult, male, female, untreatment SRA: SRR15422672

Clustering Result

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
2 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
3 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
4 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
5 Progenitors f3 (f3) marker DOI:10.1038/s41559-021-01580-3
5 Progenitors ptn (ptn) marker DOI:10.1038/s41559-021-01580-3
5 Progenitors slc1a2 (slc1a2) marker DOI:10.1038/s41559-021-01580-3
5 Progenitors cebpd (cebpd) marker DOI:10.1038/s41559-021-01580-3
6 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
7 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
8 Microglia apoc1 (apoc1) marker DOI:10.1038/s41559-021-01580-3
9 Macrophages cxcr4 (cxcr4) marker DOI:10.1038/s41559-021-01580-3
9 Macrophages ncf2 (ncf2) marker DOI:10.1038/s41559-021-01580-3
10 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
11 Oligodendrocytes cldn19 (cldn19) marker DOI:10.1038/s41559-021-01580-3
11 Oligodendrocytes cda (cda) marker DOI:10.1038/s41559-021-01580-3
12 Leukocytes cxcr4 (cxcr4) marker DOI:10.1038/s41559-021-01580-3
12 Leukocytes rps12 (rps12) marker DOI:10.1038/s41559-021-01580-3
13 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
14 Lymphocyte cells tfpi2 (tfpi2) marker DOI:10.1038/s41559-021-01580-3
15 Ciliated pde6d (pde6d) marker DOI:10.1038/s41559-021-01580-3
15 Ciliated insm1 (insm1) marker DOI:10.1038/s41559-021-01580-3
15 Ciliated vim (vim) marker DOI:10.1038/s41559-021-01580-3
15 Ciliated pde9a (pde9a) marker DOI:10.1038/s41559-021-01580-3
16 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
17 Leukocytes cxcr4 (cxcr4) marker DOI:10.1038/s41559-021-01580-3
17 Leukocytes rps12 (rps12) marker DOI:10.1038/s41559-021-01580-3
18 Erythroid cells gpx1 (gpx1) marker DOI:10.1038/s41559-021-01580-3

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
2 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
3 Progenitors f3 (f3) marker DOI:10.1038/s41559-021-01580-3
3 Progenitors ptn (ptn) marker DOI:10.1038/s41559-021-01580-3
3 Progenitors slc1a2 (slc1a2) marker DOI:10.1038/s41559-021-01580-3
3 Progenitors cebpd (cebpd) marker DOI:10.1038/s41559-021-01580-3
4 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
5 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
6 Leukocytes cxcr4 (cxcr4) marker DOI:10.1038/s41559-021-01580-3
6 Leukocytes rps12 (rps12) marker DOI:10.1038/s41559-021-01580-3
7 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
8 Microglia apoc1 (apoc1) marker DOI:10.1038/s41559-021-01580-3
9 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
10 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
11 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
12 Macrophages cxcr4 (cxcr4) marker DOI:10.1038/s41559-021-01580-3
12 Macrophages ncf2 (ncf2) marker DOI:10.1038/s41559-021-01580-3
13 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
14 Ciliated pde6d (pde6d) marker DOI:10.1038/s41559-021-01580-3
14 Ciliated insm1 (insm1) marker DOI:10.1038/s41559-021-01580-3
14 Ciliated vim (vim) marker DOI:10.1038/s41559-021-01580-3
14 Ciliated pde9a (pde9a) marker DOI:10.1038/s41559-021-01580-3
15 Oligodendrocytes cldn19 (cldn19) marker DOI:10.1038/s41559-021-01580-3
15 Oligodendrocytes cda (cda) marker DOI:10.1038/s41559-021-01580-3
16 Ependymal krt18 (krt18) marker DOI:10.1038/s41559-021-01580-3
17 Progenitors f3 (f3) marker DOI:10.1038/s41559-021-01580-3
17 Progenitors ptn (ptn) marker DOI:10.1038/s41559-021-01580-3
17 Progenitors slc1a2 (slc1a2) marker DOI:10.1038/s41559-021-01580-3
17 Progenitors cebpd (cebpd) marker DOI:10.1038/s41559-021-01580-3
18 Erythroid cells gpx1 (gpx1) marker DOI:10.1038/s41559-021-01580-3
19 Oligodendrocyte precursor cells timp4 (timp4) marker DOI:10.1038/s41559-021-01580-3
20 Lymphocyte cells tfpi2 (tfpi2) marker DOI:10.1038/s41559-021-01580-3

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
2 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
3 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
4 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
5 Progenitors f3 (f3) marker DOI:10.1038/s41559-021-01580-3
5 Progenitors ptn (ptn) marker DOI:10.1038/s41559-021-01580-3
5 Progenitors slc1a2 (slc1a2) marker DOI:10.1038/s41559-021-01580-3
5 Progenitors cebpd (cebpd) marker DOI:10.1038/s41559-021-01580-3
6 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
7 Microglia apoc1 (apoc1) marker DOI:10.1038/s41559-021-01580-3
8 Oligodendrocytes cldn19 (cldn19) marker DOI:10.1038/s41559-021-01580-3
8 Oligodendrocytes cda (cda) marker DOI:10.1038/s41559-021-01580-3
9 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
10 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
11 Leukocytes cxcr4 (cxcr4) marker DOI:10.1038/s41559-021-01580-3
11 Leukocytes rps12 (rps12) marker DOI:10.1038/s41559-021-01580-3
12 Macrophages cxcr4 (cxcr4) marker DOI:10.1038/s41559-021-01580-3
12 Macrophages ncf2 (ncf2) marker DOI:10.1038/s41559-021-01580-3
13 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
14 Ciliated pde6d (pde6d) marker DOI:10.1038/s41559-021-01580-3
14 Ciliated insm1 (insm1) marker DOI:10.1038/s41559-021-01580-3
14 Ciliated vim (vim) marker DOI:10.1038/s41559-021-01580-3
14 Ciliated pde9a (pde9a) marker DOI:10.1038/s41559-021-01580-3
15 Progenitors f3 (f3) marker DOI:10.1038/s41559-021-01580-3
15 Progenitors ptn (ptn) marker DOI:10.1038/s41559-021-01580-3
15 Progenitors slc1a2 (slc1a2) marker DOI:10.1038/s41559-021-01580-3
15 Progenitors cebpd (cebpd) marker DOI:10.1038/s41559-021-01580-3
16 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
17 Lymphocyte cells tfpi2 (tfpi2) marker DOI:10.1038/s41559-021-01580-3
18 Oligodendrocyte precursor cells timp4 (timp4) marker DOI:10.1038/s41559-021-01580-3
19 Ependymal krt18 (krt18) marker DOI:10.1038/s41559-021-01580-3
20 Erythroid cells gpx1 (gpx1) marker DOI:10.1038/s41559-021-01580-3

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
2 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
3 Progenitors f3 (f3) marker DOI:10.1038/s41559-021-01580-3
3 Progenitors ptn (ptn) marker DOI:10.1038/s41559-021-01580-3
3 Progenitors slc1a2 (slc1a2) marker DOI:10.1038/s41559-021-01580-3
3 Progenitors cebpd (cebpd) marker DOI:10.1038/s41559-021-01580-3
4 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
5 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
6 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
7 Macrophages cxcr4 (cxcr4) marker DOI:10.1038/s41559-021-01580-3
7 Macrophages ncf2 (ncf2) marker DOI:10.1038/s41559-021-01580-3
8 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
9 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
10 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
11 Microglia apoc1 (apoc1) marker DOI:10.1038/s41559-021-01580-3
12 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
13 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
14 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
15 Oligodendrocytes cldn19 (cldn19) marker DOI:10.1038/s41559-021-01580-3
15 Oligodendrocytes cda (cda) marker DOI:10.1038/s41559-021-01580-3
16 Leukocytes cxcr4 (cxcr4) marker DOI:10.1038/s41559-021-01580-3
16 Leukocytes rps12 (rps12) marker DOI:10.1038/s41559-021-01580-3
17 Erythroid cells gpx1 (gpx1) marker DOI:10.1038/s41559-021-01580-3
18 Neuron rtn1 (rtn1) marker DOI:10.1038/s41559-021-01580-3
19 Ciliated pde6d (pde6d) marker DOI:10.1038/s41559-021-01580-3
19 Ciliated insm1 (insm1) marker DOI:10.1038/s41559-021-01580-3
19 Ciliated vim (vim) marker DOI:10.1038/s41559-021-01580-3
19 Ciliated pde9a (pde9a) marker DOI:10.1038/s41559-021-01580-3
20 Oligodendrocyte precursor cells timp4 (timp4) marker DOI:10.1038/s41559-021-01580-3
21 Ependymal krt18 (krt18) marker DOI:10.1038/s41559-021-01580-3
22 Ciliated pde6d (pde6d) marker DOI:10.1038/s41559-021-01580-3
22 Ciliated insm1 (insm1) marker DOI:10.1038/s41559-021-01580-3
22 Ciliated vim (vim) marker DOI:10.1038/s41559-021-01580-3
22 Ciliated pde9a (pde9a) marker DOI:10.1038/s41559-021-01580-3

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Neuron ENSDARG00000033655 (stmn1b) marker DOI:10.1038/s41559-021-01580-3
2 Neuron ENSDARG00000099744 (gap43) marker DOI:10.1038/s41559-021-01580-3
3 Neuron ENSDARG00000020609 (snap25a) marker DOI:10.1038/s41559-021-01580-3
4 Ciliated ENSDARG00000058734 (prdx1) marker DOI:10.1038/s41559-021-01580-3
5 Neuron ENSDARG00000020609 (snap25a) marker DOI:10.1038/s41559-021-01580-3
6 Progenitors ENSDARG00000056729 (her4.2) marker DOI:10.1038/s41559-021-01580-3
7 Macrophages ENSDARG00000058389 (ccl19a.1) marker DOI:10.1038/s41559-021-01580-3
8 Oligodendrocyte precursor cells ENSDARG00000033845 (igsf9ba) marker DOI:10.1038/s41559-021-01580-3
9 Endothelium ENSDARG00000035810 (rgcc) marker DOI:10.1038/s41559-021-01580-3
10 Neuron ENSDARG00000038574 (scg2b) marker DOI:10.1038/s41559-021-01580-3
11 Microglia ENSDARG00000092170 (apoc1) marker DOI:10.1038/s41559-021-01580-3
12 Ependymal ENSDARG00000067831 (tbata) marker DOI:10.1038/s41559-021-01580-3
13 Erythroid cells ENSDARG00000071361 (si:ch211-197g15.10) marker DOI:10.1038/s41559-021-01580-3
14 Lymphocyte cells ENSDARG00000102100 (mrc1a) marker DOI:10.1038/s41559-021-01580-3
15 Oligodendrocytes ENSDARG00000077257 (timd4) marker DOI:10.1038/s41559-021-01580-3